Short- and Long-Term Mortality of Hospitalized Patients With Autoimmune Rheumatic Diseases and Serious Infections: A National Cohort Study.

OBJECTIVE: Infectious conditions are a significant cause of mortality in autoimmune rheumatic diseases (ARD). Among patients hospitalized with an infection, we compared in-hospital and long-term (3-year) mortality between those with and without ARD. METHODS: This retrospective analysis included members of the largest health maintenance organization in Israel, aged > 18 years at the first episode of infection, who required hospitalization during 2003-2019. We compared in-hospital mortality and the results of a 3-year landmark analysis of those who survived the index hospitalization between patients with ARD, according to disease subgroups, and patients without ARD. Additionally, we compared mortality outcomes among patients with ARD, according to subgroup diagnosis, matched in a 1:3 ratio by age, sex, and ethnicity to patients without ARD. RESULTS: Included were 365,247 patients who were admitted for the first time with the diagnosis of a serious infection. Of these, we identified 9755 with rheumatoid arthritis (RA), 1351 with systemic lupus erythematosus, 2120 with spondyloarthritis (SpA), 584 with systemic sclerosis, and 3214 with vasculitis. In a matched multivariate analysis, the risk for in-hospital mortality was lower among patients with RA (odds ratio [OR] 0.89, 95% CI 0.81-0.97) and SpA (OR 0.77, 95% CI 0.63-0.94). In a similar analysis, the risk of 3-year mortality was lower among patients with RA (hazard ratio [HR] 0.82, 95% CI 0.78-0.86) and vasculitis (HR 0.86, 95% CI 0.80-0.93). CONCLUSION: Among patients hospitalized for an infection, the risk of in-hospital and 3-year mortality was not increased among those with ARD compared to those without ARD.

The Diagnostic profile and clinical course of patients with rheumatic diseases in the medical intensive care unit.

Background/aim: Immunosuppressive and immunomodulatory treatments developed in recent years as a result of a better understanding of the pathophysiology of systemic rheumatic diseases (SRDs) improve the prognosis. Despite medical advances, individuals with SRDs at any stage may require intensive care and have a high mortality rate. The aim of this study was to investigate the demographic and clinical characteristics of patients with rheumatic diseases admitted to the intensive care unit (ICU), and the factors associated with the risk of mortality. Materials and methods: This was a retrospective, cross-sectional study that included patients with rheumatic diseases in the medical ICU. Factors of ICU 28-day mortality were identified by multiple-variable logistic analysis. Results: A total of 127 patients with SRDs admitted to the medical ICU were enrolled. Systemic lupus erythematosus (SLE) (32.3%) was the most common diagnosis of SRDs in patients admitted to the ICU. The reasons for admission to the ICU were combined infection and primary SRD flare-up (35.4%), primary SRD flare-up (22%), SRD-unrelated reasons (22%), infection (17.3%), drug side effects (3.9%), and SRD-related complications (0.8%). The most common organ dysfunctions before (49.6%) and during (77.2%) admission to ICU were in the respiratory system. The 28-day mortality was 78 (61.4%). While the maximum procalcitonin, serum lactate, and blood urea nitrogen (BUN) levels were higher in the nonsurvivor group, the platelet and serum albumin levels were statistically significantly lower than those in the survivor group (p < 0.05). Acute respiratory failure (ARF), the presence of septic shock, the need for invasive mechanical ventilation (IMV), BUN level, and low platelet-lymphocyte ratio (PLR) were significant in the final multiple-variable model. Conclusion: Significant predictors of mortality in patients with rheumatic diseases may include ARF, septic shock, the need for IMV, and high BUN and low PLR levels.

COVID-19 infection, admission and death among people with rare autoimmune rheumatic disease in England: results from the RECORDER project.

OBJECTIVES: To calculate the rates of COVID-19 infection and COVID-19-related death among people with rare autoimmune rheumatic diseases (RAIRD) during the first wave of the COVID-19 pandemic in England compared with the general population. METHODS: We used Hospital Episode Statistics to identify all people alive on 1 March 2020 with ICD-10 codes for RAIRD from the whole population of England. We used linked national health records (demographic, death certificate, admissions and PCR testing data) to calculate rates of COVID-19 infection and death up to 31 July 2020. Our primary definition of COVID-19-related death was mention of COVID-19 on the death certificate. General population data from Public Health England and the Office for National Statistics were used for comparison. We also describe COVID-19-related hospital admissions and all-cause deaths. RESULTS: We identified a cohort of 168 680 people with RAIRD, of whom 1874 (1.11%) had a positive COVID-19 PCR test. The age-standardized infection rate was 1.54 (95% CI: 1.50, 1.59) times higher than in the general population. A total of 713 (0.42%) people with RAIRD died with COVID-19 on their death certificate and the age-sex-standardized mortality rate for COVID-19-related death was 2.41 (2.30-2.53) times higher than in the general population. There was no evidence of an increase in deaths from other causes in the RAIRD population. CONCLUSIONS: During the first wave of COVID-19 in England, people with RAIRD had a 54% increased risk of COVID-19 infection and more than twice the risk of COVID-19-related death compared with the general population. These increases were seen despite shielding policies.

Short- and long-term prognosis of acute critically ill patients with systemic rheumatic diseases: A retrospective multicentre study.

ABSTRACT: Patients with systemic rheumatic disease (SRD) share the risks of multi-organ flare-up, cardiovascular diseases, and immunosuppression. Such situations can lead to an acute critical illness. The present study describes the clinical features of SRD patients admitted to the intensive care unit (ICU) and their short- and long- term mortality.We performed a multicentre retrospective study in 10 French ICU in Lyon, France. Inclusion criteria were SRD diagnosis and admission for an acute organ failure. The primary endpoint was ICU mortality.A total of 271 patients were included. SRD included systemic lupus erythematosus (23.2% of included patients), vasculitis (10.7%), systemic sclerosis (10.7%), idiopathic inflammatory myopathy (6.3%), and other connective tissue disorders (rheumatoid arthritis, Sjögren and Sharp syndromes; 50.9%). Initial organ failure(s) were shock (43.5% of included patients), acute kidney injury (30.5%), and acute respiratory failure (23.2%). The cause(s) of ICU admission included sepsis (61.6%), cardiovascular events (33.9%), SRD-flare up (32.8%), and decompensations related to comorbidities (28%). The ICU mortality reached 14.3%. The factors associated with ICU mortality were chronic cardiac failure, invasive ventilation and admission in ICU for another reason than sepsis or SRD flare-up. The median follow-up after ICU discharge was 33.6 months. During follow-up, 109 patients died. The factors associated with long-term mortality included age, Charlson comorbidity index, and ICU admission for sepsis or SRD flare-up.The ICU mortality of patients with SRD was low. Sepsis was the first cause of admission. Cardiovascular events and comorbidities negatively impacted ICU mortality. Admission for sepsis or SRD flare-up exerted a negative effect on the long-term outcome.

The Influence of Corticosteroids, Immunosuppressants and Biologics on Patients With Inflammatory Bowel Diseases, Psoriasis and Rheumatic Diseases in the Era of COVID-19: A Review of Current Evidence.

Patients with inflammatory bowel disease, psoriasis or other rheumatic diseases treated with corticosteroids, immunomodulators and biologics might face additional risk during COVID-19 epidemic due to their immunocompromised status. However, there was still no unanimous opinion on the use of these therapy during COVID-19 epidemic. Current studies suggested that systemic corticosteroids might increase the risk of hospitalization, as well as risks of ventilation, ICU, and death among patients with immune-mediated inflammatory diseases. Anti-TNF agent was associated with lower rate of hospitalization, as well as lower risks of ventilation, ICU, and death. No significant changes in rates of hospitalization, ventilation, ICU and mortality were observed in patients treated with immunomodulators or biologics apart from anti-TNF agents. The underlying mechanism of these results might be related to pathway of antiviral immune response and cytokine storm induced by SARS-COV-2 infection. Decision on the use of corticosteroids, immunomodulators and biologics should be made after weighing the benefits and potential risks based on individual patients.

COVID-19 Among Patients With Inflammatory Rheumatic Diseases.

BACKGROUND: The course of novel coronavirus disease 2019 (COVID-19) has been of special concern in patients with inflammatory rheumatic diseases (IRDs) due to the immune dysregulation that may be associated with these diseases and the medications used for IRDs, that may affect innate immune responses. OBJECTIVE: In this cohort study, we aimed to report the disease characteristics and variables associated with COVID-19 outcome among Turkish patients with IRDs. METHODS: Between April and June, 2020, 167 adult IRD patients with COVID-19 were registered from 31 centers in 14 cities in Turkey. Disease outcome was classified in 4 categories; (i) outpatient management, (ii) hospitalization without oxygen requirement, (iii) hospitalization with oxygen requirement, and (iv) intensive care unit (ICU) admission or death. Multivariable ordinal logistic regression analysis was conducted to determine variables associated with a worse outcome. RESULTS: 165 patients (mean age: 50 ± 15.6 years, 58.2% female) were included. Twenty-four patients (14.5%) recovered under outpatient management, 141 (85.5%) were hospitalized, 49 (30%) required inpatient oxygen support, 22 (13%) were treated in the ICU (17 received invasive mechanic ventilation) and 16 (10%) died. Glucocorticoid use (OR: 4.53, 95%CI 1.65-12.76), chronic kidney disease (OR: 12.8, 95%CI 2.25-103.5), pulmonary disease (OR: 2.66, 95%CI 1.08-6.61) and obesity (OR: 3.7, 95%CI 1.01-13.87) were associated with a worse outcome. Biologic disease-modifying antirheumatic drugs (DMARDs) do not seem to affect COVID-19 outcome while conventional synthetic DMARDs may have a protective effect (OR: 0.36, 95%CI 0.17-0.75). Estimates for the associations between IRD diagnoses and outcome were inconclusive. CONCLUSIONS: Among IRD patients with COVID-19, comorbidities and glucocorticoid use were associated with a worse outcome, while biologic DMARDs do not seem to be associated with a worse outcome.

Factors associated with COVID-19-related death in people with rheumatic diseases: results from the COVID-19 Global Rheumatology Alliance physician-reported registry.

OBJECTIVES: To determine factors associated with COVID-19-related death in people with rheumatic diseases. METHODS: Physician-reported registry of adults with rheumatic disease and confirmed or presumptive COVID-19 (from 24 March to 1 July 2020). The primary outcome was COVID-19-related death. Age, sex, smoking status, comorbidities, rheumatic disease diagnosis, disease activity and medications were included as covariates in multivariable logistic regression models. Analyses were further stratified according to rheumatic disease category. RESULTS: Of 3729 patients (mean age 57 years, 68% female), 390 (10.5%) died. Independent factors associated with COVID-19-related death were age (66-75 years: OR 3.00, 95% CI 2.13 to 4.22; >75 years: 6.18, 4.47 to 8.53; both vs ≤65 years), male sex (1.46, 1.11 to 1.91), hypertension combined with cardiovascular disease (1.89, 1.31 to 2.73), chronic lung disease (1.68, 1.26 to 2.25) and prednisolone-equivalent dosage >10 mg/day (1.69, 1.18 to 2.41; vs no glucocorticoid intake). Moderate/high disease activity (vs remission/low disease activity) was associated with higher odds of death (1.87, 1.27 to 2.77). Rituximab (4.04, 2.32 to 7.03), sulfasalazine (3.60, 1.66 to 7.78), immunosuppressants (azathioprine, cyclophosphamide, ciclosporin, mycophenolate or tacrolimus: 2.22, 1.43 to 3.46) and not receiving any disease-modifying anti-rheumatic drug (DMARD) (2.11, 1.48 to 3.01) were associated with higher odds of death, compared with methotrexate monotherapy. Other synthetic/biological DMARDs were not associated with COVID-19-related death. CONCLUSION: Among people with rheumatic disease, COVID-19-related death was associated with known general factors (older age, male sex and specific comorbidities) and disease-specific factors (disease activity and specific medications). The association with moderate/high disease activity highlights the importance of adequate disease control with DMARDs, preferably without increasing glucocorticoid dosages. Caution may be required with rituximab, sulfasalazine and some immunosuppressants.

Association of Race and Ethnicity With COVID-19 Outcomes in Rheumatic Disease: Data From the COVID-19 Global Rheumatology Alliance Physician Registry.

OBJECTIVE: Racial/ethnic minorities experience more severe outcomes of coronavirus disease 2019 (COVID-19) in the general US population. This study was undertaken to examine the association between race/ethnicity and COVID-19 hospitalization, ventilation status, and mortality in people with rheumatic disease. METHODS: US patients with rheumatic disease and COVID-19 were entered into the COVID-19 Global Rheumatology Alliance physician registry between March 24, 2020 and August 26, 2020 were included. Race/ethnicity was defined as White, African American, Latinx, Asian, or other/mixed race. Outcome measures included hospitalization, requirement for ventilatory support, and death. Multivariable regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) adjusted for age, sex, smoking status, rheumatic disease diagnosis, comorbidities, medication use prior to infection, and rheumatic disease activity. RESULTS: A total of 1,324 patients were included, of whom 36% were hospitalized and 6% died; 26% of hospitalized patients required mechanical ventilation. In multivariable models, African American patients (OR 2.74 [95% CI 1.90-3.95]), Latinx patients (OR 1.71 [95% CI 1.18-2.49]), and Asian patients (OR 2.69 [95% CI 1.16-6.24]) had higher odds of hospitalization compared to White patients. Latinx patients also had 3-fold increased odds of requiring ventilatory support (OR 3.25 [95% CI 1.75-6.05]). No differences in mortality based on race/ethnicity were found, though power to detect associations may have been limited. CONCLUSION: Similar to findings in the general US population, racial/ethnic minorities with rheumatic disease and COVID-19 had increased odds of hospitalization and ventilatory support. These results illustrate significant health disparities related to COVID-19 in people with rheumatic diseases. The rheumatology community should proactively address the needs of patients currently experiencing inequitable health outcomes during the pandemic.

Impact of COVID-19 on vulnerable patients with rheumatic disease: results of a worldwide survey.

OBJECTIVE: There is emerging evidence that COVID-19 disproportionately affects people from racial/ethnic minority and low socioeconomic status (SES) groups. Many physicians across the globe are changing practice patterns in response to the COVID-19 pandemic. We sought to examine the practice changes among rheumatologists and what they perceive the impact to be on their most vulnerable patients. METHODS: We administered an online survey to a convenience sample of rheumatologists worldwide during the initial height of the pandemic (between 8 April and 4 May 2020) via social media and group emails. We surveyed rheumatologists about their opinions regarding patients from low SES and racial/ethnic minority groups in the context of the COVID-19 pandemic. Mainly, what their specific concerns were, including the challenges of medication access; and about specific social factors (health literacy, poverty, food insecurity, access to telehealth video) that may be complicating the management of rheumatologic conditions during this time. RESULTS: 548 rheumatologists responded from 64 countries and shared concerns of food insecurity, low health literacy, poverty and factors that preclude social distancing such as working and dense housing conditions among their patients. Although 82% of rheumatologists had switched to telehealth video, 17% of respondents estimated that about a quarter of their patients did not have access to telehealth video, especially those from below the poverty line. The majority of respondents believed these vulnerable patients, from racial/ethnic minorities and from low SES groups, would do worse, in terms of morbidity and mortality, during the pandemic. CONCLUSION: In this sample of rheumatologists from 64 countries, there is a clear shift in practice to telehealth video consultations and widespread concern for socially and economically vulnerable patients with rheumatic disease.

Clinical analysis of macrophage activation syndrome in adult rheumatic disease: A multicenter retrospective study.

AIM: To evaluate the clinical and laboratory characteristics, prognostic factors, and outcome of adult rheumatic disease-associated macrophage activation syndrome (MAS). METHOD: A multicenter retrospective study was performed across 4 tertiary hospitals in China between January 1, 2017 to December 31, 2019. RESULTS: There were 61 rheumatic disease patients with MAS enrolled into this retrospective clinical study. Fever and hyperferritinemia are the most frequent clinical feature and laboratory abnormality in MAS patients. Serum ferritin > 6000 ng/mL (odds ratio [OR] = 9.46, 95% CI = 2.53-47.13, P = .005) and hemophagocytosis in bone marrow smear (OR = 11.12, 95%, CI = 3.29-50.65, P = .001) were the 2 most prominent predictive factors indicating MAS occurrence. The 90-day all-cause mortality rate of all rheumatic disease patients with MAS was 22.9% (hazards ratio [HR] = 2.15, 95% CI = 0.81-6.78, P = .05). Platelets < 100 × 109 /L (HR = 3.23, 95% CI = 2.51-4.81, P = .01) and ferritin > 6000ng/mL (HR = 6.12, 95% CI = 2.93-16.27, P = .005) were independent predictors of poor outcome in rheumatic disease-associated MAS. CONCLUSION: Macrophage activation syndrome could be a fatal complication in rheumatic disease. Patients presenting with unexplained fever, serum ferritin > 6000 ng/mL, hepatosplenomegaly and cytopenia at baseline should raise the suspicion of MAS. The presence of serum ferritin > 6000 ng/mL, hepatosplenomegaly and low number of platelets was associated with poor outcome.

Effects of hydroxychloroquine treatment on QT interval.

BACKGROUND: Hydroxychloroquine (HCQ) has been promoted as a potential treatment of coronavirus disease 2019 (COVID-19), but there are safety concerns. OBJECTIVE: The purpose of this study was to determine the effects of HCQ treatment on QT interval. METHODS: We retrospectively studied the electrocardiograms of 819 patients treated with HCQ for rheumatologic diseases from 2000 to 2020. The primary outcome was corrected QT (QTc) interval, by Bazett formula, during HCQ therapy. RESULTS: Mean patient age was 64.0 ± 10.9 years, and 734 patients (90%) were men. Median dosage of HCQ was 400 mg daily, and median (25th-75th percentile) duration of HCQ therapy was 1006 (471-2075) days. Mean on-treatment QTc was 430.9 ± 31.8 ms. In total, 55 patients (7%) had QTc 470-500 ms, and 12 (1.5%) had QTc >500 ms. Chronic kidney disease (CKD), history of atrial fibrillation (AF), and heart failure were independent risk factors for prolonged QTc. In a subset of 591 patients who also had a pretreatment electrocardiogram, mean QTc increased from 424.4 ± 29.7 ms to 432.0 ± 32.3 ms (P <.0001) during HCQ treatment. Of these patients, 23 (3.9%) had either prolongation of QTc >15% or on-treatment QTc >500 ms. Over median 5.97 (3.33-10.11) years of follow-up, 269 patients (33%) died. QTc >470 ms during HCQ treatment was associated with a greater mortality risk (hazard ratio 1.78; 95% confidence interval 1.16-2.71; P = .008) in univariable but not in multivariable analysis. CONCLUSION: HCQ is associated with QT prolongation in a significant fraction of patients. The risk of QT prolongation is higher among patients with CKD, AF, and heart failure, who may benefit from greater scrutiny.

Cardio-Rheumatology: Cardiovascular Complications in Systemic Autoimmune Rheumatic Diseases / Is Inflammation the Common Link and Target?

In the current Thematic Issue of Current Vascular Pharmacology (CVP), entitled "Systemic Autoimmune Rheumatic Diseases and Cardiology", presented in two parts, Part 1 and Part 2, review articles are included from specialists in cardiology, rheumatology, immunology and related fields. These reviews discuss the cardiovascular complications of the main systemic Autoimmune Rheumatic Diseases (ARDs). For example, the underlying pathogenetic mechanisms, the role of cardiovascular imaging and recommendations for prevention and management. These articles place inflammation as the key process, linking cardiovascular complications with ARDs. From all these reviews, the conclusion is the need for collaboration between the disciplines of Rheumatology and Cardiology to establish the emerging field of Cardio- Rheumatology. This will aid to fine-tune risk stratification and optimize preventive strategies and pharmacological therapies for patients with ARDs.

Clinical characteristics and outcomes of patients with coronavirus disease 2019 (COVID-19) and rheumatic disease: a comparative cohort study from a US 'hot spot'.

OBJECTIVE: To investigate differences in manifestations and outcomes of coronavirus disease 2019 (COVID-19) infection between those with and without rheumatic disease. METHODS: We conducted a comparative cohort study of patients with rheumatic disease and COVID-19 (confirmed by severe acute respiratory syndrome coronavirus 2 PCR), compared in a 1:2 ratio with matched comparators on age, sex and date of COVID-19 diagnosis, between 1 March and 8 April 2020, at Partners HealthCare System in the greater Boston, Massachusetts area. We examined differences in demographics, clinical features and outcomes of COVID-19 infection. The main outcomes were hospitalisation, intensive care admission, mechanical ventilation and mortality. RESULTS: We identified 52 rheumatic disease patients with COVID-19 (mean age, 63 years; 69% female) and matched these to 104 non-rheumatic disease comparators. The majority (39, 75%) of patients with rheumatic disease were on immunosuppressive medications. Patients with and without rheumatic disease had similar symptoms and laboratory findings. A similar proportion of patients with and without rheumatic disease were hospitalised (23 (44%) vs 42 (40%)), p=0.50) but those with rheumatic disease required intensive care admission and mechanical ventilation more often (11 (48%) vs 7 (18%), multivariable OR 3.11 (95% CI 1.07 to 9.05)). Mortality was similar between the two groups (3 (6%) vs 4 (4%), p=0.69). CONCLUSIONS: Patients with rheumatic disease and COVID-19 infection were more likely to require mechanical ventilation but had similar clinical features and hospitalisation rates as those without rheumatic disease. These findings have important implications for patients with rheumatic disease but require further validation.

One-Year Outcome of Critically Ill Patients With Systemic Rheumatic Disease: A Multicenter Cohort Study.

BACKGROUND: Critically ill patients with systemic rheumatic disease (SRD) have benefited from better provision of rheumatic and critical care in recent years. Recent comprehensive data regarding in-hospital mortality rates and, most importantly, long-term outcomes are scarce. RESEARCH QUESTION: The aim of this study was to assess short and long-term outcome of patients with SRD who were admitted to the ICU. STUDY DESIGN AND METHODS: All records of patients with SRD who were admitted to ICU between 2006 and 2016 were reviewed. In-hospital and one-year mortality rates were assessed, and predictive factors of death were identified. RESULTS: A total of 525 patients with SRD were included. Causes of admission were most frequently shock (40.8%) and acute respiratory failure (31.8%). Main diagnoses were infection (39%) and SRD flare-up (35%). In-hospital and one-year mortality rates were 30.5% and 37.7%, respectively. Predictive factors that were associated with in-hospital and one-year mortalities were, respectively, age, prior corticosteroid therapy, simplified acute physiology score II ≥50, need for invasive mechanical ventilation, or need for renal replacement therapy. Knaus scale C or D and prior conventional disease modifying antirheumatic drug therapy was associated independently with death one-year after ICU admission. INTERPRETATION: Critically ill patients with SRD had a fair outcome after an ICU stay. Increased age, prior corticosteroid therapy, and severity of critical illness were associated significantly with short- and long-term mortality rates. The one-year mortality rate was also associated with prior health status and conventional disease modifying antirheumatic drug therapy.

Cardiovascular Consequences of Autoimmune Rheumatic Diseases.

The increased risk of cardiovascular disease (CVD) among patients with autoimmune rheumatic diseases such as rheumatoid arthritis, spondyloarthritis and systemic lupus erythematosus has been extensively documented. Sub-clinical atherosclerosis can be assessed using various non-invasive imaging techniques. However, the mechanisms underlying the higher risk of atherosclerotic CVD in patients with autoimmune rheumatic diseases are not fully known, although they seem to include chronic low-grade systemic inflammation leading to prolonged endothelial activation, accompanied by a pro-thrombotic/pro-coagulant and autoantibody state. Furthermore, sub-clinical atherosclerosis is also influenced by other traditional risk factors for CVD. Including the individual components of the metabolic syndrome (MetS: obesity, impaired glucose metabolism, dyslipidemia and high blood pressure), the degree of which is higher in these patients than in controls. The aim of this narrative review is to discuss the CV manifestations and risk factors involved in the increased risk of CVD among patients with autoimmune rheumatic diseases.

The impact of rheumatological disorders on lymphomas and myeloma: a report on risk and survival from the UK's population-based Haematological Malignancy Research Network.

BACKGROUND: Autoimmune inflammatory disease increases the risk of diffuse large B-cell lymphoma (DLBCL) and marginal zone lymphoma (MZL), but findings for other mature B-cell malignancies are equivocal. Furthermore, it has been suggested that the increase in DLBCL is due to the activated B-cell (ABC) subtype; but data on this, and the impact of inflammatory co-morbidities on survival, are sparse and contradictory. METHODS: Data are from an established UK population-based cohort. Patients (n = 6834) diagnosed between 01/2009 and 08/2015 are included; DLBCL (n = 1771), myeloma (n = 1760), chronic lymphocytic leukaemia (CLL, n = 1580), MZL (n = 936), and follicular lymphoma (FL, n = 787). Information on rheumatological disorders and deaths was obtained by record-linkage to nationally compiled Hospital Episode Statistics, with age-and sex-matched individuals (n = 68,340) from the same catchment population (˜4 million people) providing the comparator. RESULTS: Significantly increased risks for DLBCL (OR = 2.3, 95% CI 1.8-2.8) and MZL (OR = 2.0, 95% CI 1.5-2.7) were found for those with rheumatological disorders; the site distribution of those with/without rheumatological conditions differing for DLBCL (p = 0.007) and MZL (p = 0.002). No increases in risk were observed for the remaining mature B-cell malignancies, and no associations with survival were detected for DLBCL (age-adjusted HR = 1.2, 95% CI 0.9-1.6) or MZL (age-adjusted HR = 1.0, 95% CI 0.6-1.9). Furthermore, whilst our findings provide evidence for an association with rheumatological disease severity for DLBCL, they offer little support for the notion that the association is driven by an increase in the incidence of the ABC subtype. CONCLUSION: Our findings support the hypothesis that the chronic activation and proliferation of specific B-cell populations which characterize autoimmune disease increase the potential for the lymphomagenic events that lead to DLBCL and MZL in both males and females; but have no impact on the development of CLL, FL or MM, or on survival.

The Association between Absence of Abdominal Pain and Mortality in Lower Intestinal Perforation in Patients with Autoimmune Rheumatic Diseases.

OBJECTIVE: To determine mortality and predictive factors for lower intestinal perforation (LIP) among patients with autoimmune rheumatic diseases. METHODS: This retrospective, single-center, observational study analyzed mortality rates in 31 autoimmune rheumatic disease patients with LIP who were admitted to our hospital from January 2002 to June 2017. The primary outcome was the mortality rate during hospitalization. RESULTS: The median age at the time of LIP was 61 years, and the survival rate at discharge was 64.5%. Eleven patients died of sepsis during hospitalization. Cox univariable analysis for mortality during hospitalization showed that absence of abdominal pain (hazard ratio (HR) 5.61, 95% confidence interval (CI) 1.38-22.9), higher age (HR 1.06, 95% CI 1.01-1.11), chronic kidney disease (HR 6.89, 95% CI 1.85-25.7), systemic vasculitis (HR 3.95, 95% CI 1.14-13.6), higher blood urea nitrogen (HR 1.02, 95% CI 1.01-1.04), higher serum creatinine (HR 1.41, 95% CI 1.06-1.87), and LIP due to malignancy (HR 14.3, 95% CI 1.95-105.1) significantly increased mortality. CONCLUSION: Abdominal pain was absent in 16% of LIP patients with autoimmune rheumatic diseases, and this absence was a poor prognostic factor in this cohort. Moreover, higher age, chronic kidney disease, systemic vasculitis, and LIP due to malignancy were associated with significantly increased mortality. Physicians should be aware of LIP in autoimmune disease patients with higher age, chronic kidney diseases, or systemic vasculitis even if patients reveal mild abdominal symptoms.

Effectiveness and safety of lower dose sulfamethoxazole/trimethoprim therapy for Pneumocystis jirovecii pneumonia in patients with systemic rheumatic diseases: A retrospective multicenter study.

OBJECTIVES: To evaluate the effectiveness and safety of lower-dose sulfamethoxazole/trimethoprim therapy (SMX/TMP) for Pneumocystis jirovecii pneumonia (PCP) in patients with systemic rheumatic diseases. METHODS: In this multicenter retrospective study, we compared effectiveness and safety of SMX/TMP for the treatment of PCP among patients divided into three groups according to the initial dosage of SMX/TMP: the low, ≤10 mg/kg/day; the intermediate, 10-15 mg/kg/day; and the high and conventional, 15-20 mg/kg/day for TMP dose. RESULTS: Eighty-one patients, including 22, 30, and 29 patients in the low-, the intermediate- and the high-dose group could be analyzed and the 30-day survival rate were 100%, 93.3%, and 96.7%, respectively (P = 0.28). There were significant dose-dependent increasing trends of severe adverse drug reactions (ADRs) for SMX/TMP that were graded as ≥3 according to the Common Terminology Criteria for Adverse Events. When stratified by presence of severe hypoxemia defined by alveolar-arterial O2 gradient ≥45 mmHg, the 30-day survival and treatment modification rate were similar among the three groups, but frequency of severe ADRs were significantly decreased in the low-dose group. The low-dose group was independently and negatively associated with treatment modification within 14 days and severe ADRs. CONCLUSIONS: Lower dose SMX/TMP therapy with ≤10 mg/kg/day for TMP was as effective as higher dose therapy for the treatment of PCP and associated with lower rates of treatment modification and severe ADRs in patients with systemic rheumatic diseases.

Mortality in autoimmune rheumatic diseases with anti-Ro/SSA antibody in Korea: Single center-based retrospective study.

AIM: The clinical importance of the anti-Ro antibody has not been completely understood. This study investigated identification of the association between mortality and clinical features in patients with autoimmune rheumatic diseases and detectable anti-Ro antibody titers. METHODS: We retrospectively analyzed a total of 336 patients with autoimmune rheumatic diseases and positive anti-Ro antibody titers from January 2012 to January 2015. Clinical manifestations and other autoantibodies detected during the follow-up period were identified. Cumulative survival rates were assessed by Kaplan-Meier analysis. Differences between survival curves for each risk factor were analyzed by log-rank test. The relative risk of mortality was assessed using standardized mortality ratios (SMRs). RESULTS: There was no difference in the mortality rates of patients with autoimmune rheumatic diseases with or without detectable anti-Ro antibody (SMR: 1.373, 95% CI: 0.539-2.791). Six patients (4 with systemic lupus erythematosus [SLE] and two with Sjögren's syndrome [SS]) died during the follow-up period. In the whole study population, the mortality rate of patients with lymphopenia was higher than those without lymphopenia (P = 0.023). In a sub-group of patients with both SLE and SS, Kaplan-Meier analysis showed that lymphopenia and interstitial lung disease were associated with increased mortality (P = 0.024 and P = 0.023, respectively). CONCLUSION: This study demonstrated that presence of the anti-Ro antibody was not associated with increased mortality in patients with autoimmune rheumatic disease. Conversely, we found that lymphopenia was independently associated with mortality in patients with autoimmune rheumatic disease.